US8975239B2ActiveUtilityA1

Combinations of sapacitabine or CNDAC with DNA methyltransferase inhibitors such as decitabine and procaine

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Assignee: CYCLACEL LTDPriority: Jun 9, 2008Filed: Aug 6, 2013Granted: Mar 10, 2015
Est. expiryJun 9, 2028(~1.9 yrs left)· nominal 20-yr term from priority
Inventors:Simon GreenRuth MackayIan Fleming
A61P 43/00A61P 35/02A61P 35/00A61K 31/7068A61K 31/405A61K 31/245A61K 31/353A61K 45/06A61K 31/502A61K 31/706A61K 2300/00
87
PatentIndex Score
16
Cited by
88
References
15
Claims

Abstract

A first aspect of the invention relates to a combination comprising a DNA methyltransferase inhibitor and 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof. A second aspect of the invention relates to a pharmaceutical product comprising a DNA methyltransferase inhibitor and 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect of the invention relates to a method of treating a proliferative disorder, said method comprising simultaneously, sequentially or separately administering a DNA methyltransferase inhibitor and 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, to a subject.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. A method of treating acute myelogenous leukemia, said method comprising administering to a subject, simultaneously, sequentially or separately, 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, and a DNA methyltransferase inhibitor selected from azacitidine, decitabine and zebularine. 
     
     
       2. A method according to  claim 1  which comprises administering said DNA methyltransferase inhibitor to a subject prior to sequentially or separately administering 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, to said subject. 
     
     
       3. A method according to  claim 1  which comprises administering 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, to a subject prior to sequentially or separately administering a DNA methyltransferase inhibitor to said subject. 
     
     
       4. A method according to any one of  claims 1  to  3  wherein the DNA methyltransferase inhibitor is decitabine. 
     
     
       5. A method according to any one of  claims 1  to  3  wherein the metabolite of 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine is 1-(2-C-cyano-2-deoxy-β-D-arabino-pentafuranosyl)-cytosine. 
     
     
       6. A method according to any one of  claims 1  to  3  wherein the DNA methyltransferase inhibitor and 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, are each administered in a therapeutically effective amount with respect to the individual components. 
     
     
       7. A method according to any one of  claims 1  to  3  wherein the DNA methyltransferase inhibitor and 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, are each administered in a subtherapeutic amount with respect to the individual components. 
     
     
       8. A method according to  claim 2 , wherein the DNA methyltransferase inhibitor is administered at least 72 hours before the 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof. 
     
     
       9. A method according to  3 , wherein the 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof is administered at least 24 hours before the DNA methyltransferase inhibitor. 
     
     
       10. A method according to  claim 8  or  9 , wherein the 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof is administered orally. 
     
     
       11. A method according to  claim 10 , wherein the 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof is administered in an amount of from 50 to 1000 mg per dose. 
     
     
       12. A method according to  claim 8  or  9 , wherein the DNA methyltransferase inhibitor is administered intravenously. 
     
     
       13. A method according to  claim 12 , wherein the DNA methyltransferase inhibitor is administered in an amount of between 10 to 500 mg of active ingredient per dose. 
     
     
       14. A method according to  claim 11 , wherein the DNA methyltransferase inhibitor is decitabine. 
     
     
       15. A method according to  claim 13 , wherein the DNA methyltransferase inhibitor is decitabine.

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